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Review
. 2025 Jan 28;17(3):441.
doi: 10.3390/cancers17030441.

Heterogeneity in Cancer

William J MacDonald  1   2   3 , Connor Purcell  1   2   3 , Maximilian Pinho-Schwermann  1   2   3 , Nolan M Stubbs  1   3   4 , Praveen R Srinivasan  1   2   3 , Wafik S El-Deiry  1   2   3   5   6
Affiliations
Review

Heterogeneity in Cancer

William J MacDonald et al. Cancers (Basel). .

Abstract

Cancer heterogeneity is a major challenge in oncology, complicating diagnosis, prognostication, and treatment. The clinical heterogeneity of cancer, which leads to differential treatment outcomes between patients with histopathologically similar cancers, is attributable to molecular diversity manifesting through genetic, epigenetic, transcriptomic, microenvironmental, and host biology differences. Heterogeneity is observed between patients, individual metastases, and within individual lesions. This review discusses clinical implications of heterogeneity, emphasizing need for personalized approaches to overcome challenges posed by cancer's diverse presentations. Understanding of emerging molecular diagnostic and analytical techniques can provide a view into the multidimensional complexity of cancer heterogeneity. With over 90% of cancer-related deaths associated with metastasis, we additionally explore the role heterogeneity plays in treatment resistance and recurrence of metastatic lesions. Molecular insights from next-generation sequencing, single-cell transcriptomics, liquid biopsy technology, and artificial intelligence will facilitate the development of combination therapy regimens that can potentially induce lasting and even curative treatment outcomes.

Keywords: cancer heterogeneity; drug resistance; epigenetics.

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Conflict of interest statement

W.S.E.-D. is a co-founder of Oncoceutics, Inc., a subsidiary of Chimerix. Dr. El-Deiry has disclosed his relationship with Oncoceutics/Chimerix and potential conflict of interest to his academic institution/employer and is fully compliant with the NIH and the institutional policy that is managing this potential conflict of interest.

Figures

Figure 1
Figure 1
Layers of heterogeneity in cancer.
Figure 2
Figure 2
Overview of cancer heterogeneity and emerging technologies.
See this image and copyright information in PMC

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